The relationships between physiological functions of membranes and the relevant molecular structures will be studied, with special emphasis on the plasma membrane. Major goals are to define the molecular mechanisms responsible for cell-cell recognition and adhesion, solute transport, and the interactions between the plasma membrane and certain hormones and toxic substances. Exploratory experiments will also be conducted on related phenomena, such as the regulation of adenylate cyclase by certain solute transport systems, and the potential role of cell surface carbohydrates in growth control and motility. Many of the proposed studies will use liver cell membranes isolated for normal embryonic and fully differentiated hepatocytes, hepatomas, and regenerating liver cells. Other eukaryotic cells will be used, including adipocytes, intestinal mucosa, and normal and transformed tissue culture cell lines. The glucose transport systems of enteric bacteria will be examined in detail. These systems offer a rare opportunity for reconstructing functional units of the plasma membrane from their homogeneous components; the results should provide a precise molecular description of the structure-function relationships of this class of membrane proteins, and how they interact with cytoplasmic and other membrane proteins (adenylate cyclase, other solute transport systems). The structural studies will also provide the necessary background for future structure-function experiments to be conducted with plasma membrane components involved in adhesion, hormone and toxin binding, etc., following their isolation and identification. The wide variety of techniques to be applied to the biological systems include the use of fluorescent and electron spin resonance probes, and the results will be correlated with hydro-dynamic, equilibrium and kinetic measurements on the same systems. The proposed work should yield information on the molecular mechanisms responsible for these physiological functions of the plasma membrane, and how and whether they change in malignancy, metastasis, and in normal embryonic development.